The influence of FcRn on albumin-fused and targeted drugs

Abstract

Albumin escapes intracellular degradation by binding to the neonatal Fc receptor (FcRn), which results in a very long serum half-life of nearly 3 weeks in humans. The broadly expressed FcRn is unique in that it binds both its ligands, immunoglobulin G (IgG) and albumin, in a strictly pH-dependent fashion, and this has proven to be fundamental for rescue from degradation. Further, elucidation of the biology of FcRn as well as its relationship with albumin is necessary to obtain a better understanding of how albumin homeostasis is regulated. This will be of great importance for optimal applications of albumin as a therapeutic molecule. Indeed, albumin is attracting increasing interest as it is utilized to extend the serum half-life of drugs and improve pharmacokinetics. We review the current status of albumin-based therapeutics in light of FcRn biology and the prospect of a new generation of albumin molecules with improved binding to FcRn.